This protocol has three aims: 1) To define how dietary amino acids are utilized by the splanchnic bed in the fed state, including the role of insulin and glucagon in mediating splanchnic bed utilization of amino acids. 2) To define the role of glucagon in disposal of amino acids, particularly glutamine and alanine for production of glucose. 3) To define whether theraputic analogues of cortisol used for treatment of inflammation and immune suppression affect resting energy expenditure as we have defined for cortisol. Splanchnic bed utilization of amino acids: We determined that, as in previous work with 15 N tracer, almost all of the glutamate,13 C tracer (96+/-1%) was sequestered directly in the first pass and oxidized to CO2. These results indicate that the primary fate of dietary glutamate is uptake and oxidation by the splanchnic bed. Surprisingly the fate of the iv infused glutamate tracer was also oxidation, indicating that the splanchnic bed is also responsible for removal of most of the glutamate in the blood. Cortisol: We have also completed studies to define whether synthetic analogues of cortisol such as prednisolone, an injectable analogue of prednisone, produce increases in energy expenditure as induced by cortisol. In the present study, we placed subjects on a well-defined liquid-formula diet and measured by indirect calorimetry morning REE in subjects after an overnight infusion of saline, cortisol, or the synthetic, prednisolone. Both cortisol and prednisolone increased REE significantly by 7%. These results indicate that patients who are placed on synthetic glucocorticoid analogues to control inflammation and other factors will be expected to have higher metabolic rates. Glucagon: The mechanism of glucagon's effect upon protein catabolism and why glucagon induces temporary hyperglycemia but persistant hypoaminoacidemia have not been explained. We have postulated that the waning of the glucagon induced hyperglycemia is due to a lack of amino acid substrate for gluconeogenesis, as evidenced by the fall in plasma amino acid concentration. This hypothesis was tested by infusing subjects with amino acid and glucose tracers under conditions of basal and increased glucagon levels. The glucagon infusion stimulated the glucose transiently and in a dose-dependent manner due to an increase in glucose production. The essential amino acid tracers, phenylalanine and leucine, did not demonstrate a significant change in amino acid release from proteolysis. Glucagon infusion caused a dose-dependent decrement in glutamine concentration that did not reach a steady state by the end of the studies. The fall in concentration was due to an increased rate of glutamine removal and a decrement in glutamine appearance. Glutamine is an important gluconeogenic substrate produced from other amino acids. These results indicate that although glucagon stimulates liver glucose production, it does not stimulate muscle and other protein stores to release amino acids for gluconeogenesis. The core laboratory was used in the development of methods for this protocol.